title: Effects of salicylate on the inflammatory genes expression and synaptic ultrastructure in the cochlear nucleus of rats.
abstract: Aspirin (salicylate), as a common drug that is frequently used for long-term treatment in a clinical setting, has the potential to cause reversible tinnitus. However, few reports have examined the inflammatory cytokines expression and alteration of synaptic ultrastructure in the cochlear nucleus (CN) in a rat model of tinnitus. The tinnitus-like behavior of rats were detected by the gap prepulse inhibition of acoustic startle (GPIAS) paradigm. We investigated the expression levels of the tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), N-methyl D-aspartate receptor subunit 2A (NR2A) mRNA and protein in the CN and compared synapses ultrastructure in the CN of tinnitus rats with normal ones. GPIAS showed that rats with long-term administration of salicylate were experiencing tinnitus, and the mRNA and protein expression levels of TNF-α and NR2A were up-regulated in chronic treatment groups, and they returned to baseline 14 days after cessation of treatment. Furthermore, compared to normal rats, repetitive salicylate-treated rats showed a greater number of presynaptic vesicles, thicker and longer postsynaptic densities, increased synaptic interface curvature. These data revealed that chronic salicylate administration markedly, but reversibly, induces tinnitus possibly via augmentation of the expression of TNF-α and NR2A and cause changes in synaptic ultrastructure in the CN. Long-term administration of salicylate causes neural plasticity changes at the CN level.
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, 1665 Kongjiang Road, Shanghai, 200092, China.
authors.forename: Shou-Sen
authors.initials: SS
authors.lastname: Hu
authors.forename: Ling
authors.initials: L
authors.lastname: Mei
authors.forename: Jian-Yong
authors.initials: JY
authors.lastname: Chen
authors.forename: Zhi-Wu
authors.initials: ZW
authors.lastname: Huang
authors.forename: Hao
authors.initials: H
authors.lastname: Wu
mesh_terms: D000818:Animals; D001522:Behavior, Animal; D017626:Cochlear Nucleus / Q000276:immunology / Q000378:metabolism* / Q000648:ultrastructure; D004195:Disease Models, Animal; D005786:Gene Expression Regulation; D018836:Inflammation Mediators / Q000378:metabolism*; D015850:Interleukin-6 / Q000235:genetics / Q000378:metabolism; D008297:Male; D009473:Neuronal Plasticity; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D016194:Receptors, N-Methyl-D-Aspartate / Q000235:genetics / Q000378:metabolism; D013216:Reflex, Startle; D020156:Salicylic Acid; D013569:Synapses / Q000276:immunology / Q000378:metabolism* / Q000648:ultrastructure; D013997:Time Factors; D014012:Tinnitus / Q000139:chemically induced* / Q000235:genetics / Q000276:immunology / Q000473:pathology / Q000523:psychology; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism
chemical_list: D018836:Inflammation Mediators; D015850:Interleukin-6; D012333:RNA, Messenger; D016194:Receptors, N-Methyl-D-Aspartate; D020156:Salicylic Acid; D014409:Tumor Necrosis Factor-alpha